ArticleBMC cancer2025
A genetically encoded fluorescent sensor enables sensitive and specific detection of IDH mutant associated oncometabolite D-2-hydroxyglutarate.
Article in BMC cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Recent Advances on Sensor Technologies for the Monitoring of Tumor Markers.Molecules (Basel, Switzerland) · 2026Review
- Astrocytes in neuroinflammation and brain cancer.Molecular biomedicine · 2026Review
- A genetically encoded biosensor for point-of-care and live-cell detection of D-2-hydroxyglutarate.Nature communications · 2025Article
- Review
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
D-2-hydroxyglutarate (D-2-HG) is an oncometabolite that accumulates due to mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2). D-2-HG may be used as a surrogate marker for IDH1/2 mutant cancers, yet simple and specific methods for D-2-HG detection are limited. Here, we present the development and characterization of a genetically encoded fluorescent sensor of D-2-HG (D2HGlo). D2HGlo responds to clinically relevant concentrations of D-2-HG, demonstrates exceptional selectivity and can quantify D-2-HG in various body fluids and glioma tumor supernatants. Additionally, analysis of tumor lysates using D2HGlo accurately predicted the IDH mutational status of gliomas. The successful quantification of D-2-HG within contrived samples suggests that D2HGlo may facilitate the detection and monitoring of IDH mutant cancers through liquid biopsies following further validation. In addition to D2HGlo's potential clinical utility, we also present findings for its adaptation to the cellular environment. To assess D-2-HG production in living immortalized glioma cells, we engineered D2HGlo sensors that localize to subcellular compartments, which yielded findings of elevated D-2-HG in the cytosol, mitochondria, and nucleus of IDH1 mutant cells. D2HGlo was used to perform a side-by-side comparison of cytosolic and secreted D-2-HG to reveal that glycolysis, but not glutamine catabolism, drives D-2-HG production in IDH1 mutant cells.
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